search
Back to results

Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma

Primary Purpose

Oral Cancer, VEGFR2 Inhibitor, Programmed Cell Death 1 Inhibitor

Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Camrelizumab
Apatinib
Radical surgery
Post-operative radiotherapy/chemoradiotherapy
Sponsored by
Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Eastern cooperative oncology group performance status (ECOG PS) score: 0-2 points
  • Pathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheeks, mouth floor, hard palate, posterior molar region)
  • Clinical stage of III/IVA (AJCC 2018)
  • Blood routine: white blood cells> 3,000/mm3, hemoglobin> 8g/L, platelets> 80,000/mm3
  • Liver function: Alanine Transaminase/Aspartate Transaminase <2.5 times the upper limit of normal, bilirubin <1.5 times the upper limit of normal
  • Renal function: serum creatinine <1.5 times the upper limit of normal
  • Sign the informed consent

Exclusion Criteria:

  • There are still unresolved toxic reactions above CTCAE level 2 caused by previous anti-cancer treatment
  • Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena cava syndrome, heart disease of grade 2 or higher diagnosed according to the classification criteria of the New York Heart Association (NYHA) 3 months before enrollment]
  • Active severe clinical infection (> CTCAE 5.0 version 2 infection)
  • Difficult to control hypertension (systolic blood pressure> 150 mmHg and / or diastolic blood pressure> 90 mmHg) or cardiovascular disease with clinical significance (such as activity)-such as cerebrovascular accident (≤ 6 months before randomization), myocardial infarction (≤6 months before randomization), unstable angina, New York Cardiology Society (NYHA Appendix 5) congestive heart failure grade II or above, or severe arrhythmia that cannot be controlled with drugs or has potential impact on experimental treatment
  • Women during pregnancy or lactation
  • Participated in other clinical studies within 30 days before enrollment
  • Other circumstances that the investigator thinks are not suitable for participating in the study

Sites / Locations

  • Shanghai Ninth People's Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Inductive therapy

Arm Description

Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.

Outcomes

Primary Outcome Measures

Major pathologic response
Major pathologic response is based on the pathological examination on the post-operative specimens after inductive therapy.

Secondary Outcome Measures

2-year overall survival
The overall survival time refers to the time from initiating inductive therapy to death due to any cause.
2-year tumor recurrence rate
The tumor recurrence rate is calculated using the number of patients with tumor recurrence divided by the total number of patients.

Full Information

First Posted
May 3, 2020
Last Updated
October 5, 2022
Sponsor
Shanghai Jiao Tong University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT04393506
Brief Title
Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma
Official Title
Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma: A Single-arm Phase I Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 23, 2020 (Actual)
Primary Completion Date
November 2, 2020 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In patients with locally advanced oral squamous cell carcinoma (OSCC), due to the large tumor burden and neck lymph node metastasis, comprehensive treatment is recommended, including surgery, radiotherapy, chemotherapy and others. Pre-operative inductive therapy can reduce tumor volume, increase organ retention rate, and reduce distant metastasis rate. Vascular endothelial growth factor (VEGF) receptor in head and neck squamous cell carcinoma is over-expressed and associated with disease invasion and poor prognosis. The use of targeted therapy against VEGF can not only inhibit tumor neovascularization, but also make the effectiveness of chemotherapeutic agents. VEGF and VEGFR are closely related to immune escape. Tumor growth requires new blood vessels to supply nutrients and oxygen, and VEGF can stimulate neovascularization. However, tumor neovascularization is often abnormal and distorted, which prevents immune active substances from reaching the tumor site. After tumor hypoxia, high expression of VEGF will induce tumor cells to express programmed cell death protein-1 (PD-1), which further leads to immune escape. Targeted drugs against angiogenesis can relieve immunosuppression to a certain extent, and theoretically have a synergistic effect with anti-PD-1 immunotherapy. The innovation of this study is the combination of immune checkpoint inhibitor, Camrelizumab, and targeted drug against VEGFR, Apatinib, as an inductive therapy to treat the patients with locally advanced OSCC, followed with radical surgery and post-operative radiotherapy/chemoradiotherapy, the major pathologic response and safety will be evaluated as the primary surrogate endpoints, the 2-year survival rate and local recurrence rate will be the second endpoints.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Cancer, VEGFR2 Inhibitor, Programmed Cell Death 1 Inhibitor, Inductive Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Inductive therapy
Arm Type
Other
Arm Description
Inductive therapy with Camrelizumab and Apatinib, followed by radical surgery and post-operative radiotherapy/chemoradiotherapy.
Intervention Type
Drug
Intervention Name(s)
Camrelizumab
Other Intervention Name(s)
Humanized anti-PD-1 inhibitor
Intervention Description
Inductive therapy with Camrelizumab of 200mg, iv, qd, on day 1, 15, 29.
Intervention Type
Drug
Intervention Name(s)
Apatinib
Other Intervention Name(s)
VEGFR2 inhibitor
Intervention Description
Inductive therapy with Apatinib of 250mg, po, qd, initiating on day 1, ending on the fifth day before surgery.
Intervention Type
Procedure
Intervention Name(s)
Radical surgery
Intervention Description
Radical surgery will be performed on the 42th-45th after initiation of inductive therapy
Intervention Type
Radiation
Intervention Name(s)
Post-operative radiotherapy/chemoradiotherapy
Intervention Description
Post-operative radiotherapy/chemoradiotherapy will be performed within 1.5 months after radical surgery, depending on the post-operative pathologic diagnosis.
Primary Outcome Measure Information:
Title
Major pathologic response
Description
Major pathologic response is based on the pathological examination on the post-operative specimens after inductive therapy.
Time Frame
One year
Secondary Outcome Measure Information:
Title
2-year overall survival
Description
The overall survival time refers to the time from initiating inductive therapy to death due to any cause.
Time Frame
Two years
Title
2-year tumor recurrence rate
Description
The tumor recurrence rate is calculated using the number of patients with tumor recurrence divided by the total number of patients.
Time Frame
Two years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eastern cooperative oncology group performance status (ECOG PS) score: 0-2 points Pathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheeks, mouth floor, hard palate, posterior molar region) Clinical stage of III/IVA (AJCC 2018) Blood routine: white blood cells> 3,000/mm3, hemoglobin> 8g/L, platelets> 80,000/mm3 Liver function: Alanine Transaminase/Aspartate Transaminase <2.5 times the upper limit of normal, bilirubin <1.5 times the upper limit of normal Renal function: serum creatinine <1.5 times the upper limit of normal Sign the informed consent Exclusion Criteria: There are still unresolved toxic reactions above CTCAE level 2 caused by previous anti-cancer treatment Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena cava syndrome, heart disease of grade 2 or higher diagnosed according to the classification criteria of the New York Heart Association (NYHA) 3 months before enrollment] Active severe clinical infection (> CTCAE 5.0 version 2 infection) Difficult to control hypertension (systolic blood pressure> 150 mmHg and / or diastolic blood pressure> 90 mmHg) or cardiovascular disease with clinical significance (such as activity)-such as cerebrovascular accident (≤ 6 months before randomization), myocardial infarction (≤6 months before randomization), unstable angina, New York Cardiology Society (NYHA Appendix 5) congestive heart failure grade II or above, or severe arrhythmia that cannot be controlled with drugs or has potential impact on experimental treatment Women during pregnancy or lactation Participated in other clinical studies within 30 days before enrollment Other circumstances that the investigator thinks are not suitable for participating in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lai-ping Zhong, PHD
Organizational Affiliation
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Ninth People's Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200011
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36104359
Citation
Ju WT, Xia RH, Zhu DW, Dou SJ, Zhu GP, Dong MJ, Wang LZ, Sun Q, Zhao TC, Zhou ZH, Liang SY, Huang YY, Tang Y, Wu SC, Xia J, Chen SQ, Bai YZ, Li J, Zhu Q, Zhong LP. A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma. Nat Commun. 2022 Sep 14;13(1):5378. doi: 10.1038/s41467-022-33080-8.
Results Reference
derived

Learn more about this trial

Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma

We'll reach out to this number within 24 hrs